Minimizing Pain During Office Intradetrussor Botox Injection

NCT ID: NCT04270526

Last Updated: 2025-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-15
• Study Completion Date: 2023-06-30

Brief Summary

This will be a prospective double-blinded randomized controlled trial comparing two pre-treatment protocols for patients undergoing intradetrussor botox injections to determine if a buffered lidocaine solution offers superior pain control.

Detailed Description

Lidocaine is a commonly used amide-type local anesthetic. Lidocaine exists as both a quaternary water soluble structure, and a tertiary lipid-soluble structure. Only the tertiary lipid-soluble structure can cross the lipid bilayer of a cell membrane and thereby enter a neurons axoplasm and induce the desired effect. The ionization constant of lidocaine is 7.7 which means that at a pH of 7.7, 50% of lidocaine is available in the tertiary lipid-soluble structure. At a physiologic pH between 7.35 and 7.45 only around 44% of lidocaine is in the tertiary lipid-soluble structure. However, for lidocaine to be stable in solution, it is typically formulated as a hydrochloride salt and the pH of most commercially available lidocaine solutions are at a pH of 6.09. In an acidic solution the majority of lidocaine is available in the quaternary water-soluble structure and at this pH only 2.5% of lidocaine is in the tertiary lipid-soluble structure. A Cochrane review found that increasing the pH of lidocaine prior to injection decreased pain and increased patient satisfaction perhaps because of the aforementioned pharmacokinetic principles.

Lidocaine is typically used as anesthetic for intradetrussor injections of onabotulinum toxin A for the treatment of refractory overactive bladder. In 2003, a technique for intradetrussor injections of onabotulinum toxin A was first described using only local anesthesia. At that time, the procedure involved intrauerthral lidocaine. The procedure has evolved since that time and currently many physicians utilize protocols with both utraurethral and intravesical lidocaine. At baseline intradetrusor onabotulinum toxin A injections are generally well tolerated and with reported mean VAS scores around 3.

For patients with refractory overactive bladder, the standard of care is intradetrussor onabotulinum toxin A injections. The standard protocol used by the investigators involves emptying the bladder then retrograde filling the bladder with a 1:1 mixture of 1% lidocaine normal saline. This solution remains in the bladder for approximately 15 minutes prior to injection. Given that urine is typically acidic and commercially available lidocaine solutions are similarly acidic, it is likely that only a fraction of intravesical lidocaine is in the active tertiary lipid-soluble form. The goal of this study is to determine if the investigators can improve the procedural pain of intradetrusor onabotulinum toxin A injections using a buffered solution compared to our standard solution.

After approval by the IRB, investigators will approach possible participants who are having intradetrussor botox injection for overactive bladder which is the standard of care for patients with refractory overactive bladder. If the patient meets eligibility criteria, consent forms will be signed and the patient will be randomized 1:1 to receive either our standard pretreatment regimen with 50 mL 1% lidocaine + 50ml of 0.9% normal saline or our buffered bicarbonate protocol with 50 mL 1% lidocaine + 45ml of 0.9% normal saline + 5 mL 8.4% sodium bicarbonate. The primary end point of this trial is to assess the pain scores measured on a Visual Analogue Scale (VAS) immediately following the procedure. Secondary end points include patient satisfaction, willingness to undergo repeat treatment and adverse events.

All subjects will be randomized 1:1 at the first intervention visit to one of the two protocols using a random block design . At the completion of the procedure, patients will be asked to complete a brief questionnaire about their experience. Patients will follow up in clinic for a post-void residual check two weeks after the procedure as is standard for our clinical practice.

Conditions

Overactive Bladder; Overactive Detrusor; Overactive Bladder Syndrome; Overactivity; Behavior; Urge Incontinence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active treatment

50 mL 1% lidocaine + 45ml of 0.9% normal saline + 5 mL 8.4% sodium bicarbonate

Group Type: ACTIVE_COMPARATOR

Bicarbonate protocol

Intervention Type: DRUG

Intradetrussor treatment with 50 mL 1% lidocaine + 45ml of 0.9% normal saline + 5 mL 8.4% sodium bicarbonate

Placebo treatment

50 mL 1% lidocaine + 50ml of 0.9% normal saline

Group Type: PLACEBO_COMPARATOR

Standard protocol

Intervention Type: DRUG

Intradetrussor treatment with 50 mL 1% lidocaine + 50ml of 0.9% normal saline

Interventions

Bicarbonate protocol

Intradetrussor treatment with 50 mL 1% lidocaine + 45ml of 0.9% normal saline + 5 mL 8.4% sodium bicarbonate

Intervention Type: DRUG

Standard protocol

Intradetrussor treatment with 50 mL 1% lidocaine + 50ml of 0.9% normal saline

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female patient
• Primary diagnosis of overactive bladder
• Failed first and second line therapy for overactive bladder
• Planning to undergo bladder botox injections

Exclusion Criteria

• Neurogenic bladder
• Urinary retention

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Boston Urogynecology Associates

OTHER

Sponsor Role: lead

Responsible Party

William D. Winkelman

Clinical Instructor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Boston Urogynecology Associates

Cambridge, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

037-2019

Identifier Type: -

Identifier Source: org_study_id